The overall goal of the proposed research is to examine the role of endometrial lysosomes in blastocyst implantation. More specificially, we intend to determine the contribution of endometrial lysosomal cathepsin D activity to mechanisms of blastocyst implantation by examining the hormonal control of the synthesis of this enzyme in the endometrium during early pregnancy. Accumulated data suggest that specific changes in this particular lysosomal enzyme during blastocyst implantation are significantly related to cellular mechanisms of this event. To determine the physiological significance of decreases in cathepsin D at the implantation site, further experiments will examine the relationship between the development of endometrial receptivity and the capability of uterine cathepsin D activity to decrease after decidualizing stimuli. Control of lysosomal function in cellular activity depends upon control of both the lysosomal content of enzymes and the properties of lysosomal membranes. Mobilization of lipid stores during blastocyst implantation and later increases in prostaglandin synthesis during decidualization may involve phospholipase activity of endometrial lysosomes. Various compounds which alter lysosomal enzyme content or membrane stability will be used in experiments to examine the contribution of lysosomal mechanisms to development of endometrial sensitivity to decidualizing stimuli and to increased rates of prostaglandin synthesis which appear to be characteristic features of later decidual cell growth and differentiation. These studies of the involvement of lysosomal enzymes in blastocyst implantation and early decidualization and an examination of the mechanisms of hormonal control of their activity should improve our understanding of the biochemistry of blastocyst implantation.